DNA加合物在吸烟所致肺动脉平滑肌细胞增殖中的作用及其机制研究

我们在国家自然科学基金项目（30470795，30570794，30871128，81070036，81070044）的资助下研究发现,吸烟可通过蛋白激酶C（PKC）和细胞外信号调节激酶（ERK）等促进肺动脉平滑肌细胞（PASMC）的增殖；同时我们也发现吸烟可导致DNA加合物BPDE等的形成。在此基础上，本项目拟研究DNA加合物对肺动脉平滑肌细胞增殖的影响及其相关机制。我们拟首先研究吸烟所产生的DNA加合物BPDE等对PASMC表遗传学（DNA甲基化和组蛋白乙酰化）的影响，然后探讨表遗传学变化是否导致了PKC和ERK等上调，并探讨AP2和NF-KB是否参加了该上调的调控过程。这是我们近年来科研工作的逻辑延伸，对于阐明吸烟致肺血管损伤及其修复、重构的发生机制具有重要的科学意义。

Under the supports of the National Natural Science Foundation (30470795, 30570794, 30871128, 81070036, 81070044), we found that smoking promoted pulmonary artery smooth muscle cells (PASMC) proliferation through protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). We also found that smoking could lead to the formation of DNA adducts such as BPDE. Based on these studies, the project intends to study the effect of DNA adducts on the proliferation of PASMC cell and its mechanism. Firstly, We will study the effect of DNA adduct BPDE produced by smoking on PASMC Epigenetics (DNA methylation and histone acetylation), and then investigate if the epigenetic changes can led to the increasing of PKC and ERK, and if AP2 and NF-KB are participated in the process of the increasing. This is our logical extension of our research works in recent years, it has important scientific significance to clarify the smoking-induced pulmonary vascular injury and repair, reconstruction mechanism.